Presented By:

Nasir Nazeer
Sequence of the Presentation
History of TB

TB Transmission

Drug-Resistant TB

TB Pathogenesis

Progression from LTBI to TB disease

Sites of TB disease

TB Classification System
Laboratory and Physical examination of TB

History of TB
History of Tubercluosis
TB has affected humans for
millennia

Historically known by a
variety of names, including:
Consumption
Wasting disease
White plague

TB was a death sentence for
many
History of TB
Scientific Discoveries in 1800s
Until mid 1800s, many
believed TB was hereditary

1865 Jean Antoine-Villemin
proved TB was contagious

1882 Robert Koch
discovered M. tuberculosis,
the bacterium that causes
TB

Germany issued a Postal stamp to give
tribute to Robert Koch
History of TB
Sanatoriums
Before TB antibiotics,
many patients were
sent to sanatoriums

Patients followed a
regimen of bed rest,
open air, and sunshine

TB patients who could
not afford sanatoriums
often died at home

Sanatorium patients resting outside
Famous personalities affected with TB
Breakthrough in the Fight Against
TB
Drugs that could kill TB bacteria
were discovered in 1940s and
1950s
Streptomycin (SM) discovered in
1943
Isoniazid (INH) and p-
aminosalicylic acid (PAS)
discovered between 1943 and
1952
TB death rates in U.S. began to
drop dramatically
Each year, fewer people got TB
Most TB sanatoriums in U.S. had
closed by mid 1970s

TB Resurgence
Increase in TB in mid 1980s

Contributing factors:
Inadequate funding for TB
control programs
HIV epidemic
Increased immigration from
countries where TB is
common
Spread in homeless shelters
and correctional facilities
Increase and spread of multi
drug-resistant TB


March 16, 1992 Newsweek Magazine Cover
1840 1920 1860 1900 1940 1960 1980 2000 1880
1993: TB cases decline due to
increased funding and enhanced
TB control efforts
Mid-1970s: Most
TB sanatoriums in
U.S. closed
1884:
First TB
sanatorium
established
in U.S.
1865:
Jean-
Antoine
Villemin
proved TB is
contagious
1943:
Streptomycin
(SM) a drug used
to treat TB is
discovered
1882:
Robert Koch discovers
M. tuberculosis
Mid-1980s:
Unexpected rise in
TB cases
1943-1952:
Two more drugs are
discovered to treat
TB: INH and PAS
TB History Timeline
TB Transmission
TB Transmission


Transmission is defined as the spread of an
organism, such as M. tuberculosis, from
one person to another.


TB Transmission
Types of Mycobacteria
There are different types of
Mycobacterium
M. tuberculosis causes most TB
cases in the world
Mycobacteria that can cause TB:
M. tuberculosis
M. bovis (the bovine tubercle
bacillus)
M. africanum (isolated from
cases in West, Central, and East
Africa)
M. microti (the "vole" bacillus,
a less virulent and rarely
encountered organism)
M. pinnipedii (a bacillus
infecting seals and sea lions in
the southern hemisphere and
recently isolated from humans)
Mycobacteria that do not cause
TB
e.g., M. avium complex

TB Transmission
TB is spread person to person
through the air via droplet
nuclei

M. tuberculosis may be expelled
when an infectious person:
Coughs
Sneezes
Speaks
Sings

Transmission occurs when
another person inhales droplet
nuclei
TB Transmission
Dots in air represent droplet nuclei containing
M. tuberculosis
Probability that TB will be
transmitted depends on:
Infectiousness of person with TB
disease
Environment in which exposure
occurred
Length of exposure
Virulence (strength) of the tubercle
bacilli

The best way to stop transmission
is to:
Isolate infectious persons
Provide effective treatment to
infectious persons as soon as possible
TB Transmission
Etiological Agent
M. tuberculosis is a rod-shaped,
non-spore-forming, thin aerobic
bacterium measuring 0.5 um to 3
um the bacilli cannot be
decolorized by acid alcohol; this
characteristic justifies their
classification as acid-fast bacilli.
Acid fastness is due mainly to the
organisms' high content of
mycolic acids, long-chain cross-
linked fatty acids, and other cell-
wall lipids
It grows slowly .
It cant tolerate heat, but It can
live in humid or dry or cold
surroundings.

Symptoms associated with the TB
Cough (2-3 weeks or more)
Coughing up blood
Chest pains
Fever
Night sweats
Feeling weak and tired
Losing weight without trying
Decreased or no appetite
If you have TB outside the lungs, you may have
other symptoms

Pathological changes of TB
Following are the different
pathological changes associated
with TB.
Infiltration
Hyperplasia
Calcification
These changes happen in different
stages of the tuberculosis
When defense system is
predominant, there are less
number of bacteria and only
hyperplasia and calcification
would happen.
When defense system is weak,
there are large number of bacteria
and only calcification would
happen.
As a result of infection, infected
areas are enlarged and
deteriorated.
Common Clinical patterns of TB
1. Primary pulmonary tuberculosis (Primary Complex
and Bronchial Lymphnod-Tuberculosis)
2. Milliary Tuberculosis (acute, subacute and
chronic hematogenous pulmonary tuberculosis)
3. Secondary pulmonary tuberculosis
Infiltrative pulmonary tuberculosis
Chronic fibrocavenous pulmonary tuberculosis
4. Tuberculous pleuritis
5. Extrapulmonary tuberculosis

Clinical Manifestations of TB
Systemic signs:
Most patients present as cases of pulmonary tuberculosis
with fever, weight loss, anorexia, fatigue, night sweats wasting.
Respiratory signs:
Cough may vary from mild to severe, and sputum may be
scant and mucoid or copious and purulent.
Hemoptysis may be due to cough of a caseous lesion or
bronchial ulceration chest pain, tachypenea ect.
Physical signs:
nonspecific.


Drug-Resistant TB
Caused by M. tuberculosis
organisms resistant to at
least one TB treatment drug

Isoniazid (INH)
Rifampin (RIF)
Pyrazinamide (PZA)
Ethambutol (EMB)

Resistant means drugs can
no longer kill the bacteria
Drug-Resistant TB
Primary Resistance Caused by person-to-person
transmission of drug-resistant organisms
Secondary Resistance Develops during TB treatment:

Patient was not
given appropriate
treatment regimen
OR
Patient did not
follow treatment regimen as
prescribed
Drug-Resistant TB
Mono-resistant Resistant to any one TB treatment drug
Poly-resistant Resistant to at least any 2 TB drugs (but not
both isoniazid and rifampin)
Multidrug
resistant
(MDR TB)
Resistant to at least isoniazid and rifampin,
the 2 best first-line TB treatment drugs
Extensively drug
resistant
(XDR TB)

Resistant to isoniazid and rifampin, PLUS
resistant to any fluoroquinolone AND at least
1 of the 3 injectable second-line drugs (e.g.,
amikacin, kanamycin, or capreomycin)
Drug-Resistant TB
TB infection and the World
TB Pathogenesis
Pathogenesis is defined as how an infection
or disease develops in the body.
TB Pathogenesis
Occurs when tubercle bacilli are
in the body, but the immune
system is keeping them under
control
Develops when immune system
cannot keep tubercle bacilli under
control
May develop very soon after
infection or many years after
infection
About 10% of all people with
normal immune systems who
have LTBI will develop TB disease
at some point in their lives
People with TB disease are often
infectious
TB Pathogenesis
Droplet nuclei containing tubercle bacilli are
inhaled, enter the lungs, and travel to small
air sacs (alveoli)
TB Pathogenesis
bronchiole
blood vessel
tubercle bacilli
alveoli
2
Tubercle bacilli multiply in alveoli, where
infection begins
TB Pathogenesis
A small number of tubercle bacilli enter
bloodstream and spread throughout body


brain
lung
kidney
bone
3
TB Pathogenesis
LTBI
special
immune cells
form a barrier
shell (in this
example,
bacilli are
in the lungs)
4
Within 2 to 8 weeks the immune system produces
special immune cells called macrophages that
surround the tubercle bacilli

These cells form a barrier shell that keeps the
bacilli contained and under control (LTBI)
TB Pathogenesis
shell breaks
down and
tubercle
bacilli escape
multiply
(in this example,
TB disease
develops in
the lungs)
and
5
If the immune system CANNOT keep tubercle bacilli
under control, bacilli begin to multiply rapidly and
cause TB disease

This process can occur in different places in the body
TB Pathogenesis
LTBI vs. TB Disease
Latent TB Infection (LTBI) TB Disease (in the lungs)
Inactive, contained tubercle bacilli in
the body
Active, multiplying tubercle bacilli in
the body
TST or blood test results usually
positive
TST or blood test results usually
positive
Chest x-ray usually normal Chest x-ray usually abnormal
Sputum smears and cultures
negative
Sputum smears and cultures may be
positive
No symptoms Symptoms such as cough, fever,
weight loss
Not infectious Often infectious before treatment
Not a case of TB A case of TB
TB Pathogenesis

Progression from LTBI to TB Disease
Progression to TB Disease
Risk of developing TB disease is highest the first 2
years after infection

People with LTBI can be given treatment to prevent
them from developing TB disease

Detecting TB infection early and providing treatment
helps prevent new cases of TB disease

Infection with HIV

Chest x-ray findings suggestive of
previous TB

Substance abuse

Recent TB infection

Prolonged therapy with
corticosteroids and other
immunosuppressive therapy, such
as prednisone and tumor necrosis
factor-alpha [TNF-] antagonists
Organ transplant

Silicosis

Diabetes mellitus

Severe kidney disease

Certain types of cancer

Certain intestinal conditions

Low body weight
Some conditions increase probability of LTBI
progressing to TB disease
Progression to TB Disease
Progression to TB Disease
People Exposed to TB
Not
TB Infected
Latent TB
Infection (LTBI)
Not
Infectious
Positive TST or
QFT-G test result
Latent TB
Infection
May go on to
develop TB
disease
Not
Infectious
Negative TST or
QFT-G test result
No
TB Infection
In an HIV-infected person,
TB can develop in one of
two ways:

Person with LTBI becomes
infected with HIV and then
develops TB disease as the
immune system is weakened

Person with HIV infection
becomes infected with M.
tuberculosis and then rapidly
develops TB disease

Progression to TB Disease
TB and HIV
Image credit: Mississippi State Department of Health
TB Pathogenesis

Sites of TB Disease
Sites of TB Disease
Bacilli may reach any part of the body, but common sites
include:
Brain
Lymph node
Pleura
Lung
Spine
Kidney
Bone
Larynx
TB Pathogenesis

TB Classification System
TB Classification System
Class Type Description
0 No TB exposure
Not infected
No history of TB exposure
Negative result to a TST or IGRA
1 TB exposure
No evidence of
infection
History of TB exposure
Negative result to a TST (given at least 8-
10 weeks after exposure) or IGRA
2 TB infection
No TB disease
Positive result to a TST or IGRA
Negative smears and cultures (if done)
No clinical or x-ray evidence of active
TB disease
Based on pathogenesis of TB
TB Classification System
Class Type Description
3 TB, clinically
active
Positive culture (if done) for M. tuberculosis Positive
result to a TST or IGRA, and clinical, bacteriological, or
x-ray evidence of TB disease
4 Previous TB
disease
(not clinically
active)
Medical history of TB disease
Abnormal but stable x-ray findings
Positive result to a TST or IGRA
Negative smears and cultures (if done)
No clinical or x-ray evidence of active TB disease
5 TB suspected Signs and symptoms of TB disease, but evaluation not
complete
Based on pathogenesis of TB

Laboratory and Physical
examination of TB
Laboratory and Physical Examination
Following methods are used for laboratory
and physical examination of TB
Chest radiography
Sputum examination
Tuberculin testing
PCR test to detect TB
TB antibody testing
Bronchoscopy
Radiology
Radiology
Chest radiography is the most important method to detect TB
TBs characteristics of a chest radiograph favor the diagnosis of
tuberculosis as following
shadows mainly in the upper zone
patchy or nodular shadows
the presence of a cavity or cavities, although these, of course, can
also occur in lung abscess, carcinoma, etc
the presence of calcification, although a carcinoma or pneumonia
may occur in an areas of the lung where there is calcification due
to tuberculosis
bilateral shadows, especially if these are in the upper zones
the persistence of the abnormal shadows without alteration in
an x-ray repeated after several weeks
this helps to exclude a diagnosis of pneumonia or other acute
infection




Primary Complex

Milliary Tuberculosis


Secondary Pulmonary TB

infiltrate
Sputum examination
There are direct smear
and culture methods.
Direct smear
examination is only
positive when a large no
of bacilli begin to
excrete
Tuberculin testing
A tuberculin skin test is done to see if you have ever had tuberculosis (TB).
The test is done by putting a small amount of TB protein (antigens) under
the top layer of skin on your inner forearm. If you have ever been exposed
to the TB bacteria (Mycobacterium tuberculosis), your skin will react to the
antigens by developing a firm red bump at the site within 2 days.

The TB antigens used in a tuberculin skin test are called purified protein
derivative (PPD). A measured amount of PPD in a shot is put under the top
layer of skin on your forearm. This is a good test for finding a TB infection.
It is often used when symptoms, screening, or testing, such as a chest X-
ray, show that a person may have TB.

A tuberculin skin test cannot tell how long you have been infected with TB.
It also cannot tell if the infection is latent (inactive) or is active and can be
passed to others.
Tuberculin testing
A reaction of less then 05nm
is considered as negative.
5-9mm is considered
positive (+)
10-19mm is considered
positive (++)
More then 20mm is
considered positive (+++)
A positive tuberculin test
indicates TB infection with or
without disease.


PCR to detect Tuberculosis
Bronchoscopy
Bronchoscopy is a technique of
visualizing the inside of
the airways for diagnostic and
therapeutic purposes. An
instrument (bronchoscope) is
inserted into the airways,
usually through the nose or
mouth. This allows the
practitioner to examine the
patient's airways for
abnormalities such as foreign
bodies, bleeding, tumors,
or inflammation. Specimens
may be taken from inside the
lungs. The construction of
bronchoscopes ranges from
rigid metal tubes with attached
lighting devices to flexible
optical fiber instruments with
real time video equipment.
White blood cells and ESR
The white blood count is usually normal.
In practice the white blood count is only
useful in a minority of cases, When the
patient is less ill and the radiological
shadowing less extensive the count is often
normal or high normal
ESR is often elevate